A QM/MM study of a nucleophilic aromatic substitution reaction catalyzed by 4-chlorobenzoyl-CoA dehalogenase.
نویسندگان
چکیده
Calculated using a QM/MM method, the free energy profile for the conversion of 4-chlorobenzoate to 4-hydroxybenzoate catalyzed by 4-chlorobenzoyl-CoA dehalogenase indicates the existence of a stable Meisenheimer complex.
منابع مشابه
QM/MM studies of the enzyme-catalyzed dechlorination of 4-chlorobenzoyl-CoA provide insight into reaction energetics.
The conversion of 4-chlorobenzoyl-CoA to 4-hydroxybenzoyl-CoA catalyzed by 4-chlorobenzoyl-CoA dehalogenase is investigated using combined QM/MM approaches. The calculated potential of mean force at the PM3/CHARMM level supports the proposed nucleophilic aromatic substitution mechanism. In particular, a Meisenheimer intermediate was found, stabilized by hydrogen bonds between the benzoyl carbon...
متن کاملDetermination of the chlorine kinetic isotope effect on the 4-chlorobenzoyl-CoA dehalogenase-catalyzed nucleophilic aromatic substitution.
The chlorine kinetic isotope effect (KIE) on the dehalogenation of 4-chlorobenzoyl-CoA catalyzed by 4-chlorobenzoyl-CoA dehalogenase has been measured at room temperature and optimal pH. The measured value of (37)k = 1.0090 +/- 0.0006 is larger than the KIEs recently measured for haloalkane and fluoroacetate dehalogenase. This indicates that the transition state for dissociation of chloride ion...
متن کاملContributions of long-range electrostatic interactions to 4-chlorobenzoyl-CoA dehalogenase catalysis: a combined theoretical and experimental study.
It is well established that electrostatic interactions play a vital role in enzyme catalysis. In this work, we report theory-guided mutation experiments that identified strong electrostatic contributions of a remote residue, namely, Glu232 located on the adjacent subunit, to 4-chlorobenzoyl-CoA dehalogenase catalysis. The Glu232Asp mutant was found to bind the substrate analogue 4-methylbenzoyl...
متن کاملIdentification of active site residues essential to 4-chlorobenzoyl-coenzyme A dehalogenase catalysis by chemical modification and site directed mutagenesis.
4-Chlorobenzoyl-coenzyme A (4-CBA-CoA) dehalogenase catalyzes the hydrolysis of 4-CBA-CoA to 4-hydroxybenzoyl-coenzyme A (4-HBA-CoA) via a nucleophilic aromatic substitution pathway involving the participation of an active site carboxylate side chain in covalent catalysis. In this paper we report on the identification of conserved aspartate, histidine, and tryptophan residues essential to 4-CBA...
متن کاملEvidence for electrophilic catalysis in the 4-chlorobenzoyl-CoA dehalogenase reaction: UV, Raman, and 13C-NMR spectral studies of dehalogenase complexes of benzoyl-CoA adducts.
This paper reports on the mechanism of substrate activation by the enzyme 4-chlorobenzoyl coenzyme A dehalogenase. This enzyme catalyzes the hydrolytic dehalogenation of 4-chlorobenzoyl coenzyme A (4-CBA-CoA) to form 4-hydroxybenzoyl coenzyme A (4-HBA-CoA). The mechanism of this reaction is known to involve attack of an active site carboxylate (Asp or Glu side chain) at C(4) of the substrate be...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Chemical communications
دوره 7 شماره
صفحات -
تاریخ انتشار 2004